Combinations of biologic agents and traditional disease modifying antirheumatic drugs (DMARDs) are being increasingly used in early RA. The effectiveness and side effects of different regimens, however, are unlikely to be compared in clinical trials performed by pharmaceutical companies. The proposed multicenter trial, Treatment of Early Aggressive Rheumatoid Arthritis (TEAR), represents the first pre-planned 5-year trial of biologic/DMARD combinations in early RA. Thus, the TEAR trial might provide information of value to RA patients, rheurnatologists and the Food & Drug Administration. The proposed trial is a 3-arm study comparing 2 different combinations (anti-TNF plus methotrexate versus methotrexate plus hydroxychloroquine plus sulfasalazine) versus monotherapy (methotrexate) in patients with early RA who have an "aggressive" clinical phenotype defined by presence of erosions on hand or feet radiographs, or positive serum rheumatoid factor, plus active synovitis of multiple joints. A steering committee of clinical researchers involved with RA trials has been formed to design the TEAR trial. The clinical trials planning grant is needed for the following specific aims: (1) to conduct meetings and conference calls of steering committee to write the grant for funding of the TEAR trial; (2) to develop study materials including data collection instruments, design and preparation for the quality control procedures, informed consent prototype, manual of operations and procedures (MOPP); (3) to secure definite commitments for participation from pharmaceutical companies and clinical research sites; (4) to design appropriate pharmacogenetic studies that potentially would identify patients who have a significant positive clinical response in this trial; and (6) to perform preliminary analysis of existing data to refine the outcomes to be used in this clinical trial.